Dataset Information

Screening and evaluation of the role of immune genes of brain metastasis in lung adenocarcinoma progression based on the TCGA and GEO databases.

ABSTRACT:

Background

Brain metastasis was one of the factors leading to the poor long-term prognosis of patients with lung adenocarcinoma (LUAD).

Methods

The expression levels of immune genes in LUAD and LUAD brain metastases tissues were analyzed in GSE161116 dataset using the GEO2R, and the levels of differential immune genes in normal lung and LUAD tissues were verified. The biological functions and signaling mechanisms of the differential immune genes were explored via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Cox regression analysis was used to screen the prognostic factors of LUAD patients, and a risk model was constructed. The role of the model was checked in the development of LUAD via receiver operating characteristic analysis, gene set enrichment analysis, and Cox regression analysis.

Results

Differentially expressed genes (DEGs) in brain metastasis were involved in the adaptive immune response, B cell differentiation, leukocyte migration, NF-kB signaling pathway, among others. The expression levels of TNFRSF11A, MS4A2, IL11, CAMP, MS4A1, and F2RL1 were independent factors affecting the poor prognosis of LUAD patients via Cox regression analysis and Akaike information criterion. In the constructed risk model, the overall survival of LUAD patients in the high-risk group was poor. The risk model was significantly related to the gender, clinical stage, T stage, lymph node metastasis, and survival status of LUAD patients. In addition, the risk model score was an independent risk factor that affected the poor prognosis of LUAD patients. TNFRSF11A, CAMP, F2RL1, IL11, MS4A1, and MS4A2 of the risk factors had diagnostic significance in LUAD brain metastasis and LUAD. The risk model participated in cytokinetic process, cell cycle, citrate cycle TCA cycle, etc. The risk model score was correlated with the levels of B cells memory, mast cells resting, macrophages M0, mast cells activated, neutrophils, eosinophils, T cells gamma delta, and immune cell markers.

Conclusions

The risk model based on the LUAD brain metastasis immune factors TNFRSF11A, MS4A2, IL11, CAMP, MS4A1, and F2RL1 was related to the diagnosis, poor prognosis, and immune infiltrating cells of LUAD patients, and is expected to provide a reference for the development of treatment strategies for LUAD patients.

SUBMITTER: Chen C

PROVIDER: S-EPMC8411151 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUNDS:Lung adenocarcinoma (LUAD) is one of the most common malignancies, and is a serious threat to human health. The aim of the present study was to assess potential biomarkers for the prognosis of LUAD through the analysis of gene expression microarrays. METHODS:The gene expression data for GSE118370 was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between normal lung and LUAD samples were screened using the R language. The DAVID database was used to analyze the functions and pathways of DEGs. The STRING database was used to the map protein-protein interaction (PPI) networks, and these were visualized with the Cytoscape software. Finally, the prognostic analysis of the hub gene in the PPI network was performed using the Kaplan-Meier tool. RESULTS:A total of 406 downregulated and 203 upregulated DEGs were identified. The GO analysis results revealed that downregulated DEGs were significantly enriched in angiogenesis, calcium ion binding and cell adhesion. The upregulated DEGs were significantly enriched in the extracellular matrix disassembly, collagen catabolic process, chemokine-mediated signaling pathway and endopeptidase inhibitor activity. The KEGG pathway analysis revealed that downregulated DEGs were enriched in neuroactive ligand-receptor interaction, hematopoietic cell lineage and vascular smooth muscle contraction, while upregulated DEGs were enriched in phototransduction. In addition, the top 10 hub genes and the most closely interacting modules of the top 3 proteins in the PPI network were screened. Finally, the independent prognostic value of each hub gene in LUAD patients was analyzed through the Kaplan-Meier plotter. Seven hub genes (ADCY4, S1PR1, FPR2, PPBP, NMU, PF4, and GCG) were closely correlated to overall survival time. CONCLUSION:The discovery of these candidate genes and pathways reveals the etiology and molecular mechanisms of LUAD, providing ideas and guidance for the development of new therapeutic approaches to LUAD.

Project description:BackgroundClear cell renal cell carcinoma (ccRCC) is a commonly occurring tumor. Through a deeper understanding of the immune regulatory mechanisms in the tumor microenvironment, immunotherapy may serve as a potential treatment for cancer patients. This study aimed at identifying the survival-related immune cells and hub genes, which could be potential targets for immunotherapy in ccRCC.MethodsThe gene expression profiles and clinical data of ccRCC patients were extracted from UCSC Xena and Gene Expression Omnibus (GEO) databases. Kaplan-Meier (KM) survival and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were utilized to select the survival-related tumor-infiltrating immune cells. Multivariate Cox regression was utilized to develop a signature based on the tumor-infiltrating immune cells (TIICs). Based on the signature, the risk score was calculated, following which the samples were divided into high-risk and low-risk groups. Differentially expressed genes (DEGs) between the two risk groups were identified. Functional enrichment analysis was performed and cytoHubba plug-in of Cytoscape was used to identify the hub genes. Multiple datasets were utilized to validate these hub genes, including the Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and the Human Protein Atlas (HPA), and the GEO datasets. Finally, a correlation analysis was performed to evaluate the relationship between the hub genes and TIICs.ResultsFour immune survival-related cells, including T cell CD4 memory-activated, T cell regulatory (Tregs), eosinophils, and mast cell resting were identified. Nine immune-specific hub genes were identified, which included APOE, CASR, CTLA4, CXCL8, EGF, F2, KNG1, MMP9, and IL6. Furthermore, these hub genes were significantly correlated with clinical traits and closely associated with some TIICs.ConclusionA total of four survival-related immune cell types and nine hub genes were found to be closely associated with ccRCC. These findings may have implications for the development of novel potential immunotherapeutic targets for ccRCC.

Project description:Background Mitophagy is used by eukaryotic cells to eliminate damaged mitochondria. The deregulation of this process can lead to an accumulation of dysfunctional mitochondria and is implicated in carcinogenesis and tumorigenesis. Despite increasing evidence that mitophagy is involved in the development of colon cancer, the role of mitophagy-related genes (MRGs) in colon adenocarcinoma (COAD) prognosis and treatment remains largely unknown. Methods Differential analysis was used to identify differentially expressed mitophagy-related genes associated with COAD and conduct key module screening. Cox regression and least absolute shrinkage selection operator, and other analyses were used to characterize prognosis-related genes and verify the feasibility of the model. The model was tested using GEO data and a nomogram was constructed for future clinical application. The level of immune cell infiltration and immunotherapy were compared between the two groups, and sensitivity to treatment with many commonly used chemotherapeutic agents was assessed in individuals with different risk factors. Finally, qualitative reverse transcription polymerase chain reaction and western blotting were performed to assess the expression of prognosis-related MRGs. Results A total of 461 differentially expressed genes were mined in COAD. Four prognostic genes, PPARGC1A, SLC6A1, EPHB2, and PPP1R17, were identified to construct a mitophagy-related gene signature. The feasibility of prognostic models was assessed using Kaplan-Meier analysis, time-dependent receiver operating characteristics, risk scores, Cox regression analysis, and principal component analysis. At 1, 3, and 5 years, the area under the receiver operating characteristic curves were 0.628, 0.678, and 0.755, respectively, for TCGA cohort, and 0.609, 0.634, and 0.640, respectively, for the GEO cohort. Drug sensitivity analysis found that camptothecin, paclitaxel, bleomycin, and doxorubicin were significantly different between low- and high-risk patients. The qPCR and western blotting results of clinical samples further confirmed the public database results. Conclusions This study successfully constructed a mitophagy-related gene signature with significant predictive value for COAD, informing new possibilities for the treatment of this disease.

Project description:BackgroundLung adenocarcinoma (LUAD) is the major cause of cancer mortality. Traditional prognostic factors have limited importance after including other parameters. Thus, developing a more credible prognostic model combined with genes and clinical parameters is necessary.MethodsThe messenger RNA (mRNA) expression and clinical information from The Cancer Genome Atlas (TCGA)-LUAD datasets and microarray data from three Gene Expression Omnibus (GEO) databases were obtained. We identified differentially-expressed genes (DEGs) between lung tumor and normal tissues through integrated analysis of the three GEO datasets. Univariate and multivariate Cox regression analyses were conducted to select survival-associated DEGs and to establish a prognostic gene signature which was associated with overall survival (OS). The expression of gene proteins was assessed in 180 LUAD tissue microarrays (TMAs) by immunohistochemistry (IHC). We verified its predictive performance with a Kaplan-Meier (KM) curve, receiver operating characteristic (ROC) curve, and Harrell's concordance index (C-index) and validated it in external GEO databases. Multivariate Cox regression analysis was performed to identify the significant prognostic indicators in LUAD. Furthermore, we established a prognostic nomogram based on TCGA-LUAD dataset.ResultsA three-gene signature was constructed to predict the OS of LUAD patients. The KM analysis, ROC curve, and C-index present a good predictive ability of the gene signature in TCGA dataset [P<0.0001; C-index 0.6375; 95% confidence interval (CI): 0.5632-0.7118; area under the ROC curve (AUC) 0.674] and the external GEO datasets (P=0.05, 0.004, and 0.04, respectively). Univariate and multivariate Cox regression analyses also verified that LUAD patients with low-risk scores had a decreased risk of death compared to those with a high-risk score in TCGA database [hazard ratio (HR) =0.3898; 95% CI: 0.1938-0.7842; P<0.05]. Finally, we constructed a nomogram integrating the gene signature and clinicopathological parameters (P<0.0001; C-index 0.762; 95% CI: 0.714-0.845; AUC 0.8136). Compared with conventional staging, a nomogram can effectively improve prognosis prediction.ConclusionsThe nomogram is closely associated to the OS of LUAD patients. This consequence may be beneficial to individualized treatment and clinical decision-making.